Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adrenal cortex contains a kallikrein-like enzyme that may lead to bradykinin (BK) formation. This study was designed to determine whether BK acts on adrenocortical cells to stimulate steroid secretion. BK, Lys-BK, a specific BK 2 (B2) receptor agonist, and desArg9-BK, a specific BK 1 (B1) receptor agonist, all stimulated aldosterone secretion from cultured bovine adrenal zona glomerulosa cells. BK and Lys-BK were equipotent (EC50 = 2 x 10(-9) M), whereas desArg9-BK was 1000-fold less potent. The maximal effects of BK and BK analogs were comparable to the maximal effects of adrenocorticotropin or angiotensin II. A B2, but not a B1, receptor antagonist inhibited BK-stimulated aldosterone release. Verapamil and N,N-diethylamino-octyl-3,4,5-trimethoxybenzoate, which reduce intracellular calcium concentrations, reduced BK-stimulated aldosterone secretion. Although BK stimulated both prostacyclin and aldosterone production, indomethacin abolished prostacyclin production without affecting aldosterone secretion. In cultured adrenal fasciculata cells, high concentrations of BK stimulated cortisol release, but B1 or B2 receptor agonists were not effective. BK-stimulated cortisol secretion was reduced by N,N-diethylamino-octyl-3,4,5-trimethoxybenzoate but not by indomethacin. In summary, BK stimulates aldosterone release from cultured adrenal glomerulosa cells via high affinity B2 receptors. The effect is calcium-dependent and independent of prostaglandins. BK also increases cortisol release; however, this stimulation requires high concentrations of BK and may be mediated by an unknown receptor or by a receptor-independent mechanism.
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PMID:Bradykinin stimulates aldosterone release from cultured bovine adrenocortical cells through bradykinin B2 receptors. 131 40

We evaluated whether the brain kallikrein-kinin system plays a role in the regulation of adrenocorticotropin (ACTH) release in rats. Intracerebroventricular (icv) injection of bradykinin (0.24 nmol) increased plasma immunoreactive ACTH (irACTH) levels (from 93 +/- 4 to 200 +/- 12 pg/ml, P less than 0.01). This effect was prevented by icv kinin antagonist at 15.4 nmol/h (from 98 +/- 5 to 108 +/- 6 pg/ml; not significant). The antagonist did not alter the increase in plasma irACTH levels induced by icv corticotropin-releasing factor (CRF), arginine vasopressin, or prostaglandin E2. Melittin (7 nmol/h icv) increased plasma irACTH from 95 +/- 4 to 268 +/- 7 pg/ml (P less than 0.01). This effect was prevented by icv kinin antagonist (15.4 nmol/h), kallikrein antibodies (13 pmol/h), or indomethacin (0.28 mmol/h). ACTH response to melittin was not altered by antagonists of CRF or vasopressin. Intra-arterial injection of insulin (0.3 IU/kg body wt) reduced plasma glucose levels to a similar extent in rats given icv kinin antagonist or vehicle; the ACTH response to insulin-induced hypoglycemia was slightly less in rats given kinin antagonist than in those given vehicle (55 +/- 5 vs. 86 +/- 4 pg/ml, P less than 0.05). The brain kallikrein-kinin system may play a role in the regulation of ACTH secretion in stimulated conditions.
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PMID:Role of brain kallikrein-kinin system in regulation of adrenocorticotropin release. 131 88

A commercially available radioimmunoassay (RIA) kit for measurement of human adrenocorticotropin (hACTH) was validated for use in dogs. Assay sensitivity was 3 pg/ml. Intra-assay coefficient of variation (x 100; CV) for 3 canine plasma pools was 3.0 (mean +/- SD, 33 +/- 0.99 pg/ml), 4.2 (71 +/- 2.4 pg/ml) and 3.7 (145 +/- 3.7 pg/ml) %. Interassay CV for 2 plasma pools measured in 6 assays was 9.8 (37 +/- 3.6 pg/ml) and 4.4 (76 +/- 3.4 pg/ml) %, respectively. Dilutional parallelism was documented by assaying 2 pools of canine plasma at 3 dilutions and correcting the measured result for dilution. Corrected mean concentrations for the first pool were 33 (+/- 0.99), 36 (+/- 4.3), and 33 (+/- 6.8) pg/ml; corrected mean concentrations for the second pool were 145 (+/- 5.4), 141 (+/- 10.8) and 125 (+/- 3.4) pg/ml. Recovery of 1-39hACTH added to canine plasma (6.25, 12.5, 25.0, 50.0, and 100.0 pg/ml) was linear and quantitative (slope = 0.890, R2 = 0.961). To test whether anticoagulant or the protease inhibitor, aprotinin, influences ACTH concentration in canine plasma, ACTH was measured in canine blood collected in 4 tubes containing anticoagulant: heparin (H), heparin + 500 kallikrein inhibitor units (KIU) of aprotinin/ml (HA), EDTA (E), and EDTA + aprotinin (EA). Plasma ACTH concentration was the same when samples containing H and HA, or HA and E were compared, and was significantly (P less than 0.01) lower in samples containing EA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of sample handling on adrenocorticotropin concentration measured in canine plasma, using a commercially available radioimmunoassay kit. 170

A vaccinia virus (VV) vector was used to express rat plasma kallikrein (rPK) in the constitutively secreting cells, BSC-40, and in the endocrine regulated cells, AtT-20. Using a specific rPK antibody and a fluorogenic substrate, Phe-Phe-Arg-AMC, we demonstrated that in both cell lines VV infections resulted in the synthesis of an immunoreactive enzyme predominantly present as a zymogen which can be activated with trypsin. Stimulation of VV:rPK-infected AtT-20 cells with either 5mM 8-bromo-cAMP or 56 mM KCl resulted in a different pattern of rPK and ACTH secretion, strongly suggesting that rPK follows the constitutive secretory pathway. Finally, the 10% rPK activity found within AtT-20 cell extracts had no effect on pro-opiomelanocortin (POMC) processing either intracellularly or extracellularly. The above data show that the biosynthetic machinery of both cell lines analyzed does not allow the efficient activation of plasma prekallikrein. Finally, despite the PK's demonstrated ability to cleave various hormone precursors in vitro at pairs of basic residues, in vivo, we did not obtain evidence that this hepatic enzyme can also act as an intracellular pro-protein processing enzyme.
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PMID:Expression and sorting of rat plasma kallikrein in POMC-producing AtT-20 cells. 185 25

The effect of adrenal steroids (mineralo- and glucocorticoids) as well as that of the adrenocorticotrophic peptide tetracosactide (beta 1-24 corticotropin) on the renal kallikrein activity and on the urinary kallikrein excretion of rats was investigated. After the animals had been adapted to metabolic cages, they were injected with deoxycorticosterone acetate (15 mg/kg day), corticosterone (40 mg/kg day), both steroids combined or the vehicle (sesame oil). Additional groups of rats received tetracosactide (0.05, 0.1 or 0.2 mg/day) or the vehicle (100 microliter of 38 X 10(-3) M ZnCl2). After four days of treatment the urinary kallikrein excretion was higher in deoxycorticosterone-treated rats than in their controls. This increase was prevented when corticosterone was administered simultaneously. The renal kallikrein activity of corticosterone as well as that of deoxycorticosterone plus corticosterone-treated rats was subnormal. A dose-related reduction of both the renal kallikrein activity and the urinary kallikrein excretion was observed 2 days after starting the tetracosactide administration. It may be concluded that a stimulation of the endogenous release of glucocorticoids in the rat reduces the renal kallikrein activity and that glucocorticoids can prevent the stimulating effect of mineralocorticoids.
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PMID:The influence of tetracosactide and adrenal steroids on renal kallikrein activity and urinary kallikrein excretion in rats. 299 96

The report of 'kallikrein-like' activity in the rat neuro-intermediate lobe (N-IL) and its possible involvement in pro-opiomelanocortin processing led us to explore the expression of the kallikrein gene(s) in the pituitary. Using 32P-labelled rat pancreatic kallikrein cDNA, we have shown positive hybridization for rat anterior pituitary poly(A)+ RNA, of identical size on Northern blots (approximately 1.0 kb) to rat kidney poly(A)+ RNA run in parallel. Prior adrenalectomy or ovariectomy decreased the level of kallikrein mRNA seen in the anterior pituitary; total RNA from rat N-IL showed no significant hybridization. On hybridization histochemistry the anterior pituitary was strongly positive, and the neural and intermediate lobes negative. The previously reported kallikrein-like activity in the N-IL is therefore probably due to a non-kallikrein kininogenase; in the anterior pituitary, kallikrein may have a physiological role in limited precursor proteolysis, but lack kininogen activity.
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PMID:Kallikrein gene expression in the rat anterior pituitary. 384 24

Human beta-endorphin was injected into the cerebrospinal fluid in rabbits by means of a needle inserted into the lateral ventricle of the brain. Control rabbits received an equal amount of saline. beta-Endorphin induced a significant pulmonary platelet trapping compared to control. beta-Endorphin had no effect on arterial blood pressure, heart rate, platelet aggregability ex vivo or fibrinolytic activity (fibrinolytic plates). The plasma activity of antithrombin III, kallikrein-like activity and kallikrein inhibitor determined by means of chromogenic substrates was not influenced by beta-endorphin.
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PMID:Beta-endorphin administered into the lateral ventricle of the brain causes pulmonary platelet trapping in rabbits. 609 38

Glucocorticoid-remediable aldosteronism (GRA) is a hereditary cause of human hypertension in which aldosterone secretion is regulated by adrenocorticotropin (ACTH). A genetic mutation which causes GRA has recently been identified in our laboratory, a hybrid or chimeric gene fusing nucleotide sequences of the 11 beta-hydroxylase and aldosterone synthase genes. The finding that these chimeric gene duplications are sensitive and specific markers for GRA allows for a simple, direct genetic test for this disorder. In preliminary studies, we found a wide range of blood pressure levels (including normotension) in affected GRA subjects. Studies to data indicate that this is not related to environmental factors such as sodium intake. Another possibility is that chimeric gene expression is variable, with low blood pressure subjects having reduced gene expression. However, the data have not demonstrated differences in steroid levels in subjects with severe versus mild hypertension. In fact, it is likely that the wide range in blood pressure levels in affected subjects involves interaction of other systems which control blood pressure. Preliminary data in two kindreds suggest that blood pressure levels are reciprocally related to levels of urinary kallikrein excretion, supporting the notion that GRA is a hypertension-predisposing syndrome, with the resultant blood pressure the interaction of the gene mutation with other blood pressure regulatory systems. Although GRA is a mineralocorticoid excess state, as evidenced by profoundly suppressed levels of plasma renin activity, we have observed (contrary to the reported literature) that normokalemia is a typical finding. In one large normokalemic pedigree, preliminary findings indicate that these subjects have a normal capacity to excrete potassium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocorticoid-remediable aldosteronism (GRA): diagnosis, variability of phenotype and regulation of potassium homeostasis. 779 15